Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A nucleoside triphosphatase (NTPase) activity appeared to be associated with a highly purified nuclear preparation from rat cardiac ventricles. Different nucleoside triphosphates (UTP greater than GTP greater than ITP greater than CTP) supported this enzymic activity, which was stimulated by Mg2+ but not by Ca2+. The nuclear NTPase activity could be down regulated by endogenous phosphorylation of a 55,000 Mr protein. Maximal phosphorylation of the 55,000 Mr protein occurred in the presence of Mg(2+)-ATP. Addition of cAMP, cGMP, Ca2+, Ca2+/phospholipid, Ca2+/calmodulin, and catalytic subunit of cAMP-dependent protein kinase was not associated with any further phosphorylation of the 55,000 Mr protein. However, in the presence of Ca2+/calmodulin or the catalytic subunit of the cAMP-dependent protein kinase additional proteins became phosphorylated, but these had no effect on the Mg(2+)-NTPase activity. These results indicate that a protein with Mr 55,000 may be involved in the regulation the Mg(2+)-NTPase activity associated with rat cardiac nuclei.
Mol Cell Biochem 1991 Apr 10
PMID:Regulation of rat cardiac nuclei-associated Mg(2+)-NTPase by phosphorylation. 165 81

Expression of the Salmonella typhimurium pyrC gene encoding dihydroorotase is negatively regulated by CTP and stimulated by GTP. This regulation does not occur at the level of transcription initiation but appears to involve translation attenuation of the transcripts. Alterations of specific bases in a region of hyphenated dyad symmetry located in the leader established that base pairing in the 5' terminal region of the pyrC leader transcript is required for normal regulation of dihydroorotase synthesis. Primer extension experiments on RNA from mutant strains that permit manipulation of the CTP and GTP pools showed that pyrC transcription may start at either a cytosine or a guanine residue, 2 bp apart. The ratio between G-starts and C-starts appeared to be determined by the intracellular [GTP]/[CTP] pool ratio. The larger transcript, starting with a C, is able to form a stable hairpin in the 5' end, sequestering part of the ribosome binding site in the stem. The leader of the shorter transcript, however, cannot form this secondary structure. Thus, translational initiation will occur unhindered only from the shorter transcript.
Mol Gen Genet 1991 Feb
PMID:Dual transcriptional initiation sites from the pyrC promoter control expression of the gene in Salmonella typhimurium. 170 67

Expression of the Escherichia coli pyrE gene is regulated by transcription attenuation in the intercistronic orfE-pyrE region and modulated by the distance between the transcribing RNA polymerase and the leading ribosome as a function of the supply of UTP and GTP. In this communication we show that pyrE expression is hyper-repressed in vivo following addition of uracil in strains carrying the nusAcs10 mutation. This phenotype, previously seen in rpsL1204 strains whose ribosomes are pseudodependent on streptomycin and work at suboptimal elongation rate, indicates that RNA polymerase escapes from the ribosomes in the pyrE attenuator region in the nusA mutant. In vitro transcription studies revealed that the build-up of the full-length attenuated orfE transcript occurred more slowly in the presence of the NusA protein than in its absence. Moreover, the NusA protein enhanced several transcription pauses through the orfE gene. These effects were more pronounced when low concentrations of either UTP or GTP were used than at low concentrations of either CTP or ATP. The results indicate that the NusA protein is required for proper regulation of pyrE gene expression and is involved, together with the NTP pools, in maintaining the coupling between transcription and translation in the pyrE attenuator region by inhibiting RNA chain elongation.
Mol Microbiol 1991 Feb
PMID:Role of transcription pausing in the control of the pyrE attenuator in Escherichia coli. 171 Mar 13

The URA7 gene of Saccharomyces cerevisiae encodes CTP synthetase (EC 6.3.4.2) which catalyses the conversion of uridine 5'-triphosphate to cytidine 5'-triphosphate, the last step of the pyrimidine biosynthetic pathway. We have cloned and sequenced the URA7 gene. The coding region is 1710 bp long and the deduced protein sequence shows a strong degree of homology with bacterial and human CTP synthetases. Gene disruption shows that URA7 is not an essential gene: the level of the intracellular CTP pool is roughly the same in the deleted and the wild-type strains, suggesting that an alternative pathway for CTP synthesis exists in yeast. This could involve either a divergent duplicated gene or a different route beginning with the amination of uridine mono- or diphosphate.
Mol Gen Genet 1991 Dec
PMID:Cloning, sequencing and characterization of the Saccharomyces cerevisiae URA7 gene encoding CTP synthetase. 175 46

The influence of an increased temperature (39 degrees C) on a denaturation of 50 kDa-fragment of myosin subfragment 1 was studied in the presence of different nucleoside triphosphates (NTP) and nucleoside diphosphates (NDP). The degree of the denaturation was appreciated evaluated from its trypsinolysis depth. According to their protective influence NTP and NDP were shown to arrange in lines ATP greater than or equal to CTP greater than UTP greater than GTP and ADP greater than GDP greater than CDP greater than UDP, correspondingly. The results received and the literature data allow to suggest that there are at least two states of ATPase site hydrophobic pocket, one of which in responsible for sharp ATPase reaction slowing-down on the stage of macroergic bonding splitting.
Mol Biol (Mosk)
PMID:[Functionally different states of the "hydrophobic pocket" of the myosin ATPase center]. 183 76

The purified Ca2+/Mg2+ ATPase from rat heart plasma membrane was activated by Ca2+ and Mg2+ with Ka values of 1.47 mM and 2.51 mM, respectively; other divalent cations also activated the enzyme but to a lesser extent. Divalent cations like Cu2+, Zn2+, Ni2+, Cd2+ were potent inhibitors of the enzyme activity in the presence of Ca2+ or Mg2+ whereas Na+, K+ or HCO3- did not affect the Ca2+/Mg2+ ATPase activity; the pH optima was 8.5. The enzyme hydrolyzed ATP with a Km of 0.34 mM for Ca2+ ATPase and 0.48 mM for Mg2+ ATPase; various nucleoside triphosphate such as ITP, CTP, GTP, and UTP were also hydrolyzed. Phospholipase A and C as well as neuraminidase decreased the Ca2+/Mg2+ ATPase activity whereas phospholipase D was ineffective. The purified Ca2+/Mg2+ ATPase was found to bind ATP-r-35S with two affinities; the KD values were 50.9 +/- 0.8 and 1160 +/- 198 nM and the Bmax values were 8.71 +/- 0.16 and 145 +/- 9.7 nmol/mg protein for high and low affinity sites, respectively. Treatment of the enzyme preparation with phospholipases and neuraminidase did not affect the ATP-r-35S binding. Ca2+ was also found to bind with Ca2+/Mg2+ ATPase with a KD of 0.384 mM and a Bmax of 1.85 mumol/mg protein; Ni2+, Mn2+, Zn2+ at 1 mM concentrations inhibited the Ca2+ binding but Mg2+ and verapamil were without effect. Phospholipase A and neuraminidase decreased the Ca2+ binding by 20-30%; this indicated that Ca2+ binding with the purified enzyme may be partly due to the phospholipids and sialic acid residues associated with the enzyme. These results show that the purified Ca2+/Mg2+ ATPase is a Ca2+ binding glycoprotein having two binding sites for ATP. Furthermore, this study suggests that phospholipids associated with purified Ca2+/Mg2+ ATPase are required for maximal activity.
Mol Cell Biochem 1991 Oct 16
PMID:Characterization of the purified rat heart plasma membrane Ca2+/Mg2+ ATPase. 183 90

The region from position -154 to position -50 upstream from the start site of transcription of the Escherichia coli rrnB P1 promoter, the upstream activator region (UAR), is required for maximal promoter activity in vivo. Maximal activation (20 to 30-fold) requires the binding of Fis protein in vitro and in vivo. However, two- to fourfold activation remains in vivo even in the absence of Fis. Here, we demonstrate that the presence of the UAR increases the rate of formation of E sigma 70-promoter complexes in vitro in the absence of added protein factors (factor-independent activation). The UAR increases the rate of the RNA polymerase concentration-dependent step in the association pathway to a stable complex formed in the presence of the initiating nucleotides ATP and CTP (RPinit). The rate of dissociation from RPinit is not affected. In addition, a supercoiled template of native superhelical density increases both the association rate for the formation of RPinit and the lifetime of complexes formed in the absence of nucleotides (RPo or open complex), but does not affect factor-independent activation. The data are consistent with a model whereby the UAR affects only the initial recognition event (closed complex formation) without affecting either the rate or extent of isomerization to the locally denatured open complex. In the accompanying paper, a variety of chemical and enzymatic probes are used to characterize RPinit and RPo both with and without the UAR.
J Mol Biol 1991 Aug 05
PMID:Factor-independent activation of Escherichia coli rRNA transcription. I. Kinetic analysis of the roles of the upstream activator region and supercoiling on transcription of the rrnB P1 promoter in vitro. 187 Jan 23

In Escherichia coli aspartate transcarbamylase, each regulatory chain is involved in two kinds of interfaces with the catalytic chains, one with the neighbour catalytic chain which belongs to the same half of the molecule (R1-C1 type of interaction), the other one with a catalytic chain belonging to the other half of the molecule (R1-C4 type of interaction). In the present work, site-directed mutagenesis was used to investigate the involvement of the C-terminal region of the regulatory chain in the process of feed-back inhibition by CTP. Removal of the two last C-terminal residues of the regulatory chains is sufficient to abolish entirely the sensitivity of the enzyme to CTP. Thus, it appears that the contact between this region and the 240s loop of the catalytic chain (R1-C4 type of interaction) is essential for the transmission of the regulatory signal which results from CTP binding to the regulatory site. None of the modifications made in the R1-C4 interface altered the sensitivity of the enzyme to the activator ATP, suggesting that the effect of this nucleotide rather involves the R1-C1 type of interface. These results are in agreement with the previously proposed interpretation that CTP and ATP do not simply act in inverse ways on the same equilibrium.
J Mol Biol 1991 Aug 05
PMID:Heterotropic interactions in Escherichia coli aspartate transcarbamylase. Subunit interfaces involved in CTP inhibition and ATP activation. 187 Jan 32

Phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4, 5-bisphosphate (PIP2), 1, 2-diglyceride (DG), lysophosphatidylcholine (LPC), and free fatty acids (FFA) contents, as well as their fatty acid composition, were measured in transient global cerebral ischemia. ATP and CTP were also studied. Male Wistar rats were subjected to 1, 5, and 30 min of ischemia and 10, 30, and 60 min of recirculation following 30 min of ischemia. In addition, for the quantification of PI, PIP, and PIP2, rats were also subjected to 30 and 60 min of recirculation following 5 min of ischemia. PIP2 and PIP decreased rapidly during 5 min of ischemia and recovered completely after recirculation. DG increased almost at the same rate during ischemia and returned to normal after recirculation. PI showed almost no changes throughout entire course. LPC increased during 5 min of ischemia and returned to normal after recirculation. Stearic acid and arachidonic acid contained in DG increased during 5 min of ischemia, whereas saturated fatty acids increased in LPC. Among the FFA accumulated during ischemia, stearic acid and arachidonic acid increased rapidly and were followed by increases of other FFA. From these results, the pathways for the increase of FFA during ischemia and the fate of FFA after recirculation are discussed. In addition, the importance of the changes of PIP, PIP2, and LPC is also discussed.
Mol Chem Neuropathol 1990 Jun
PMID:Changes of polyphosphoinositides, lysophospholipid, and free fatty acids in transient cerebral ischemia of rat brain. 196 9

Low-angle X-ray scattering in solution has been used to probe the quaternary structure of a mutant version of Escherichia coli aspartate transcarbamylase in which Glu239 of the catalytic chain was replaced by glutamine by site-directed mutagenesis. X-ray crystallographic studies of the wild-type enzyme have shown that one set of intersubunit interactions involving Glu239 are lost, and are replaced by another set of intrachain interactions when the enzyme undergoes the allosteric transition from the T to the R state. Functional analysis of the mutant enzyme with glutamine in place of Glu239 indicates that homotropic co-operativity is lost without altering the maximal specific activity. The radius of gyration of the unligated mutant enzyme is larger than the unligated wild-type, indicating an alteration in quaternary structure of the mutant. However, the radius of gyration of the mutant enzyme in the presence of N-(phosphonoacetyl)-L-aspartate (PALA) is identical with the value for the wild-type enzyme in the presence of PALA. X-ray scattering at larger angles indicates that the mutant enzyme is in a new structural state different from the wild-type T and R structures. The scattering pattern in the presence of saturating concentrations of PALA is identical with that of the wild-type R structure. Saturating concentrations of carbamyl phosphate alone are sufficient to convert most of the mutant enzyme to the R structure, in the absence of aspartate. CTP shifts the scattering pattern of the mutant enzyme in the presence of saturating carbamyl phosphate towards the scattering curve of the unligated enzyme, but CTP has no effect on the scattering curve in the absence of carbamyl phosphate or in the presence of subsaturating PALA. However, in the presence of subsaturating PALA, ATP causes a strong shift towards the R structure. Neither ATP nor CTP has any effect on the activity of the mutant enzyme. These data suggest that the replacement of Glu239 by glutamine results in a new quaternary structure. These data also explain, on a structural basis, why co-operativity is lost in this mutant enzyme.
J Mol Biol 1990 Jul 05
PMID:Structural consequences of the replacement of Glu239 by Gln in the catalytic chain of Escherichia coli aspartate transcarbamylase. 197 63


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